I 142 



HANDBOOK OF PHYSIOLOGY 



CIRCULATION II 



it quite feasible to study these parameters directly. 

 Unfortunately, these have not been much applied to 

 the problem of ions and vascular tissue. This is an 

 important deficiency. 



electrical measurements. It is now generally be- 

 lieved that electrical potentials developed across cell 

 membranes depend on ionic distribution, mobility, 

 and the permeability characteristics of the membrane 

 itself. Unfortunately, because of technical difficulties, 

 vascular tissue has not been approached until very 

 recentlv and only minimal information is available. 

 We shall thus have to lean heavily on electrical meas- 

 urements obtained from other types of smooth muscle, 

 especially guinea pig taenia coli. 



CONTINUOUS MONITORING OF Na OR K. ION ACTIVITY. 



The development of ion-specific glasses responding 

 especially to Na + or K + (55) has made it possible to 

 prepare electrodes suitable for monitoring Na + or K + 

 in flowing blood (79). These electrodes can discrimi- 

 nate ion activity with far greater resolution than any 

 methods hitherto available and can also be applied 

 to the analysis of single samples or to the continuous 

 monitoring of activity in a tissue bath. Their applica- 

 tion to the problem in hand has only just begun, but 

 already they have furnished several important pieces 

 of information. 



ROLE OF SODIUM AND POTASSIUM IN 

 VASCULAR SMOOTH MUSCLE TENSION 



Evidence from Studies of Diastolic Blood 

 Pressure or Reactivity 



GENERAL RELATION OF Na AND K TO CLINICAL AND 



experimental hypertension. More than 50 years 

 ago Ambard & Beaujard (4) suggested that the de- 

 velopment of clinical hypertension was abetted by 

 salt, although they incorrectly stressed Cl~ rather than 

 Na+. Allen & Sherrill (2) revived the idea some 25 

 years later, correctly identified Na+ as the important 

 ion, and urged the use of low salt diets in treatment. 

 After a period of neglect the idea recurred when 

 Kempner (126) advocated the unpalatable rice diet 

 for hypertensive patients and indeed, in so doing, 

 came close to starting a food cult (27). Shortly there- 

 after the main therapeutic benefit of the rice diet was 

 distinguished from its psychological benefit and shown 

 to reside in its low sodium content (34, 98, 159). By 

 the beginning of the last decade the low sodium diet 



was firmly established as a measure of limited but 

 certain usefulness in the management of the hyper- 

 tensive patient. Because of difficulties inherent in its 

 use it could not be widely applied but, even so, pa- 

 tients were routinely encouraged to reduce their 

 voluntary salt intake for fear of accelerating the prog- 

 ress of their disease. 



The effort to reduce the amount of sodium available 

 to the body in hypertension led naturally to attempts 

 to increase its loss through the kidneys. This approach 

 was dramatically successful as specific natriuretic 

 agents, such as chlorothiazide and hydrochlorothia- 

 zide, were developed and shown to be highly effective 

 in the treatment of hypertension (1, 8, 97). These 

 agents show clearly that as long as the kidneys are 

 competent, the simple desalting of the body will re- 

 duce an elevated diastolic blood pressure and, even 

 though normotensive levels may not be attained, will 

 tend to keep it down. 



Studies of experimental forms of hypertension have 

 also underlined the general relation between available 

 salt and blood pressure. This was first shown by the 

 fact that hypertension induced by the prolonged 

 administration of desoxycorticosterone acetate (DCA) 

 is accelerated by concomitantly increasing the salt 

 intake (179)- This effect was shown to be specifically 

 due to the sodium ion (180). A slower blood pressure 

 rise can be induced without adding extra salt to the 

 intake above that supplied by the food, but no rise 

 occurs if the diet is sodium-free (18, 84, 181). A similar 

 dependence on Na intake has been found to obtain 

 for the hypertension which occurs during adrenal 

 regeneration (184, 185) and in the subtotally nephrec- 

 tomized animal (128). Thus far, most forms of experi- 

 mental hypertension respond to Na deprivation or 

 depletion with a reduction in blood pressure (194). 



The implication of Na metabolism in the hyper- 

 tensive process has also been sharply underlined by 

 studies of the response of man and animals to acutely 

 imposed salt loads. The results have been strikingly 

 uniform and the accelerated excretion of such loads, 

 first systematically demonstrated in various forms of 

 hypertension in the rat (77, 93), is also a consistent 

 feature in hypertensive man (35, 94). 



There is reliable but not so extensive evidence im- 

 plicating K in a general way with the hypertensive 

 process. Most of these studies have come from M. 

 Friedman and his associates. These investigators first 

 pointed out that the rise in blood pressure produced 

 by renal compression in the rat can be reduced by 

 prolonged K deprivation (6 weeks) and argued that 

 this effect is related to the decrease in smooth muscle 



